+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion



Different host cell proteases activate the SARS-coronavirus spike-protein for cell-cell and virus-cell fusion



Virology 413(2): 265-274



Severe acute respiratory syndrome coronavirus (SARS-CoV) poses a considerable threat to human health. Activation of the viral spike (S)-protein by host cell proteases is essential for viral infectivity. However, the cleavage sites in SARS-S and the protease(s) activating SARS-S are incompletely defined. We found that R667 was dispensable for SARS-S-driven virus-cell fusion and for SARS-S-activation by trypsin and cathepsin L in a virus-virus fusion assay. Mutation T760R, which optimizes the minimal furin consensus motif 758-RXXR-762, and furin overexpression augmented SARS-S activity, but did not result in detectable SARS-S cleavage. Finally, SARS-S-driven cell-cell fusion was independent of cathepsin L, a protease essential for virus-cell fusion. Instead, a so far unknown leupeptin-sensitive host cell protease activated cellular SARS-S for fusion with target cells expressing high levels of ACE2. Thus, different host cell proteases activate SARS-S for virus-cell and cell-cell fusion and SARS-S cleavage at R667 and 758-RXXR-762 can be dispensable for SARS-S activation.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052605342

Download citation: RISBibTeXText

PMID: 21435673

DOI: 10.1016/j.virol.2011.02.020


Related references

Genetic analysis of the SARS-coronavirus spike glycoprotein functional domains involved in cell-surface expression and cell-to-cell fusion. Virology 341(2): 215-230, 2005

Cleavage inhibition of the murine coronavirus spike protein by a furin-like enzyme affects cell-cell but not virus-cell fusion. Journal of Virology 78(11): 6048-6054, 2004

Furin cleavage of the SARS coronavirus spike glycoprotein enhances cell-cell fusion but does not affect virion entry. Virology 350(2): 358-369, 2006

T-cell epitopes in severe acute respiratory syndrome (SARS) coronavirus spike protein elicit a specific T-cell immune response in patients who recover from SARS. Journal of Virology 78(11): 5612-5618, 2004

Prokaryotic expression of S2 extracellular domain of SARS coronavirus spike protein and its fusion with Hela cell membrane. Nan Fang Yi Ke Da Xue Xue Bao 29(3): 381-386, 2009

Mutational analysis of the murine coronavirus spike protein: effect on cell-to-cell fusion. Virology 214(2): 453-463, 1995

Palmitoylation of the cysteine-rich endodomain of the SARS-coronavirus spike glycoprotein is important for spike-mediated cell fusion. Virology 360(2): 264-274, 2007

Roles in cell-to-cell fusion of two conserved hydrophobic regions in the murine coronavirus spike protein. Virology 244(2): 483-494, 1998

Acquisition of cell-cell fusion activity by amino acid substitutions in spike protein determines the infectivity of a coronavirus in cultured cells. Plos one 4(7): E6130, 2009

Amino acid substitutions within the leucine zipper domain of the murine coronavirus spike protein cause defects in oligomerization and the ability to induce cell-to-cell fusion. Journal of Virology 73(10): 8152-8159, 1999

Aromatic amino acids in the juxtamembrane domain of severe acute respiratory syndrome coronavirus spike glycoprotein are important for receptor-dependent virus entry and cell-cell fusion. Journal of Virology 82(6): 2883-2894, 2008

Mutagenesis of the transmembrane domain of the SARS coronavirus spike glycoprotein: refinement of the requirements for SARS coronavirus cell entry. Virology Journal 6: 230, 2009

Cryo-EM structure of the SARS coronavirus spike glycoprotein in complex with its host cell receptor ACE2. Plos Pathogens 14(8): E1007236, 2018

Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein. Virology 335(1): 34-45, 2005

The virulence of mouse hepatitis virus strain A59 is not dependent on efficient spike protein cleavage and cell-to-cell fusion. Journal of Neurovirology 8(5): 400-410, 2002